The function of the brain relies on the precise assembly of approximately 100 billion neurons with trillions of synaptic connections. The development of neural circuitry involves a complex interplay of cell-cell adhesion, inter-neuronal signaling and assembly of intracellular macromolecular protein complexes. The three tandem-arrayed protocadherin (Pcdh) gene clusters, namely Pcdh-, Pcdh- and Pcdh-?, regulate neuronal survival and synaptic development by distinct mechanisms. In this project, we will develop a new mouse genetic model to define the overlapping function of clustered Pcdhs in circuit development, independently from their role in neuronal survival. This line of investigation will advance our understanding of molecular diversity underlying the precision of neural circuitry in the brain. PUBLIC HEALTH RELEVANCE: Molecular basis underlying the precision and complexity of mammalian neural circuits remains largely undefined. The objective of this project is to generate a new genetic tool for analyzing the function of a large family of cell surface molecules-protocadherins in the brain.